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Origins of sequence diversity in the malaria vaccine candidate merozoite surface protein-2 (MSP-2) in Amazonian isolates of Plasmodium falciparum
Authors:Hoffmann Erika H E  Malafronte Rosely S  Moraes-Avila Sandra L  Osakabe Ana Lúcia  Wunderlich Gerhard  Durham Alan M  Ribolla Paulo Eduardo M  del Portillo Hernando A  Ferreira Marcelo U
Institution:1. Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo (SP), Brazil;2. Institute of Tropical Medicine of São Paulo, University of São Paulo, 05403-000 São Paulo (SP), Brazil;3. Department of Computer Sciences, Institute of Mathematics and Statistics, University of São Paulo, 05508-900 São Paulo (SP), Brazil;4. Department of Parasitology, Institute of Biosciences of Botucatu, State University of São Paulo, 18618-000 Botucatu (SP), Brazil;5. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 01238, USA;1. National Institute of Malaria Research, Indian Council of Medical Research, Dwarka Sector-8, New Delhi 110077, India;2. National Institute of Pathology, Indian Council of Medical Research, New Delhi 110029, India;3. Department of Zoology, University of Delhi, New Delhi 110007, India;1. Agence de Médecine Preventive, 75015 Paris, France;2. School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
Abstract:The recent evolution of Plasmodium falciparum is at odds with the extensive polymorphism found in most genes coding for antigens. Here, we examined the patterns and putative mechanisms of sequence diversification in the merozoite surface protein-2 (MSP-2), a major malarial repetitive surface antigen. We compared the msp-2 gene sequences from closely related clones derived from sympatric parasite isolates from Brazilian Amazonia and used microsatellite typing to examine, in these same clones, the haplotype background of chromosome 2, where msp-2 is located. We found examples of msp-2 sequence rearrangements putatively created by nonreciprocal recombinational events, such as replication slippage and gene conversion, while maintaining the chromosome haplotype. We conclude that these nonreciprocal recombination events may represent a major source of antigenic diversity in MSP-2 in P. falciparum populations with low rates of classical meiotic recombination.
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